Lviv clinical bulletin 2016, 2(14)-3(15): 23-27

The Role of Gene of the Tumor Necrosis factor-alfa G-308A Polymorphism in the Development of Congestive Heart Failure in Patients with Ischemic Heart Disease and Obesity

P. Kravchun, O. Kadykova, N. Ryndina, S. Krapivko

Kharkiv National Medical University

Introduction. One of the widespread and prognostically unfavourable conditions in cardiovascular diseases is a congestive heart failure (CHF), where an important role is given to the proinflammatory cytokines in the pathogenesis of the disease. Polymorphic variants of the gene of tumor necrosis factor-a (TNF-a) are determinants of heightened risk in the development of CHF in patients with ischemic heart disease (IHD).

Purpose of the study is to define the role of G-308A polymorphism of tumor necrosis factor-a gene as a poten­tial factor in the development of congestive heart failure in patients with ischemic heart disease and obesity.

Materials and research methods. Within the research a complex examination of 222 patients with IHD and obesity has been performed. The experimental group included 115 patients with ischemic heart disease with a nor­mal weight. The control group included 35 apparently healthy people. The groups were contrasted according to age and sex. Patients with severe co-morbidity of the respiratory and digestive organs, kidneys, and patients with on­cology diseases were not enrolled in the clinical trial.

Clinical and instrumental testing was performed with all the patients.

The study of G-308A polymorphic locus of the gene of TNF-a was performed using the method of polymerase chain reaction with an electrophoretic detection of the results. At that, “SNP-EXPRESS” reagents kits, manufactured by Manufacturing Joint Stock Company – “Liteh” (Russian Federation), were used. DNA purification from the whole blood was performed using the reagent “DNA-express-blood” manufactured by Manufacturing Joint Stock Company – “Liteh” (Russian Federation) in concordance with the specification. The accuracy of the allocation of genotype frequencies was determined by the respondency to Hardy-Weinberg Equilibrium Calculator (pi2 + 2 pipj + pj2 = 1).

The statistical processing of the data was performed with the help of the software program burst “Statistica”, version 6,0. To compare the allocation of alleles and genotypes frequencies the Pearson and Fischer criteria were used. The proportion cast (PC) has been calculated to determine the risk ratio for the development of the diseases. PC = 1 was equaled to absence of association; PC > 1 – positive association, PC < 1 – negative association of allele or a genotype with the disease (low risk level of the development of the disease). A reliable interval represents the one within the limits of which the prognostic value is found with the probability of 95.0 %. The diversity with p < 0.05 was considered statistically reliable.

Results of the investigation and their discussion. According to the results of the research the bearers of allelic gene A of polymorphic locus G-308A of the gene of TNF-a were the nine patients from the control group, which makes 25.71 %, 41 (35.65 %) with IHD, and 89 (40.09 %) with IHD with concomitant obesity; allelic gene – 26 (74.29 %), 74 (64.35 %) and 133 (59.91 %) correspondingly. The genotype of polymorphic locus G-308A of the gene of TNF-a showed the following results in the research: the most frequent genotype in the control group was G/G – with 25 patients (71.43 %), less frequent – genotype G/A – with 8 patients (22.86 %) and only 2 patients (5.71 %) had genotype A/A. In the group of patients with ischemic heart disease (IHD) the tendency was the same: there were 56 patients (48.70 %) with a genotype G/G, 38 patients (33.04 %) – with a genotype G/A and 21 patients – with a genotype A/A; in case of IHD with concomitant obesity the results were different: the majority of the patients had the genotype G/A – 90 (40.54 %), genotype G/G – presented 74 (33.33 %) and genotype A/A – presented 58 (26.13 %).

Conclusion. The allelic gene A of polymorphic locus G-308A of the gene of tumor necrosis factor-a, which was more frequently observed with patients with the ischemic heart disease and concomitant obesity, makes a risk fac­tor for the development of congestive heart failure. The presence of the allelic gene A of polymorphic locus G-308A of the gene of tumor necrosis factor-a, which was more frequently observed with patients with the ischemic heart disease and concomitant obesity was associated with the risk reduction of the development of congestive heart failure.


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